炎性疼痛大鼠海馬5-HT水平、5-HT2A受體mRNA和BDNFmRNA的表達(dá)和作用研究及度洛西汀的干預(yù)作用
發(fā)布時(shí)間:2018-05-25 11:10
本文選題:炎性疼痛 + 海馬。 參考:《濟(jì)寧醫(yī)學(xué)院》2017年碩士論文
【摘要】:目的:疼痛引起的不愉快的情緒可以影響機(jī)體對(duì)疼痛的感知。海馬體是大腦邊緣系統(tǒng)的重要組成部分,參與處理和調(diào)整疼痛刺激,尤其是疼痛的情緒-動(dòng)機(jī)部分。海馬的形態(tài)可塑性的變化以及海馬內(nèi)神經(jīng)化學(xué)物質(zhì)的改變都與疼痛有著密切的聯(lián)系,但是具體機(jī)制沒有完全清楚。其中5-羥色胺(5-hydroxytryptamine,5-HT)以及在5-HT2A受體都參與疼痛的調(diào)解。腦源性神經(jīng)營(yíng)養(yǎng)因子(brain-derived neurotrophic factor,BDNF)能夠調(diào)節(jié)海馬內(nèi)神經(jīng)元的可塑性變化。因此本實(shí)驗(yàn)的目的是:(1)探討炎性疼痛大鼠海馬內(nèi)5-HT、5-HT2A受體mRNA和BDNFmRNA的表達(dá)的變化及其作用;(2)探討度洛西汀對(duì)炎性大鼠海馬內(nèi)5-HT、5-HT2A受體mRNA及BDNFmRNA表達(dá)的影響;(3)探討5-HT與BDNF之間的關(guān)系。方法:將72只成年的雄性SD(Sprague-Dawley)大鼠隨機(jī)分為對(duì)照組,實(shí)驗(yàn)組:炎性疼痛模型組、炎性疼痛模型+生理鹽水灌胃組和炎性疼痛模型+度洛西汀灌胃組,每組各18只。炎癥疼痛模型是向大鼠左側(cè)的足底皮下注射完全弗氏佐劑(Complete Freund’s Adjuvant,CFA)和生理鹽水(1:1)混合溶劑100μl。度洛西汀(10mg/(kg.d))灌胃2周,生理鹽水同等劑量灌胃2周。在建模前及處理2周后采用電子測(cè)痛儀檢測(cè)大鼠左側(cè)足底50%縮足閾值(paw withdrawal threshold,PWT)的變化,用糖水偏愛實(shí)驗(yàn)和強(qiáng)迫游泳實(shí)驗(yàn)檢測(cè)大鼠抑郁樣行為,采用RT-PCR檢測(cè)不同組間大鼠海馬內(nèi)5-HT2A受體mRNA和BDNFmRNA的表達(dá),ELISA檢測(cè)海馬中5-HT的變化。結(jié)果:四組大鼠在處理前,50%PWT差異無統(tǒng)計(jì)學(xué)意義。2周后炎性疼痛模型組的50%PWT和糖水消耗率與對(duì)照組比較,痛閾和糖水消耗率降低,不動(dòng)時(shí)間增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。炎性疼痛模型+度洛西汀灌胃組與炎性疼痛模型+生理鹽水灌胃組相比的50%PWT升高(P0.01),糖水消耗率升高(P0.05),不動(dòng)時(shí)間下降(P0.01)。炎性疼痛模型組與對(duì)照組相比較,海馬中的5-HT降低(P0.05),海馬中5-HT2A受體mRNA的表達(dá)均值降低,但差異無統(tǒng)計(jì)學(xué)意義(P0.05),BDNFmRNA的表達(dá)降低(P0.05)。炎性疼痛模型+度洛西汀灌胃組與炎性疼痛模型+生理鹽水灌胃組比較,海馬中的5-HT上升(P0.01),海馬中5-HT2A受體mRNA和BDNFmRNA的表達(dá)都升高(P0.05)。結(jié)論:慢性炎性疼痛大鼠出現(xiàn)的痛閾下降和抑郁樣表現(xiàn)可能與海馬內(nèi)5-HT水平和BDNFmRNA的表達(dá)下降有關(guān);度洛西汀可以提高慢性炎性疼痛大鼠的痛閾,改善抑郁樣行為,其機(jī)制可能通過海馬中5-HT、5-HT2A受體mRNA和BDNFmRNA的表達(dá)升高發(fā)揮作用;5-HT可能通過其2A受體參與BDNF的調(diào)節(jié)。
[Abstract]:Objective: pain-induced unpleasant emotions can affect the body's perception of pain. The hippocampus is an important component of the limbic system of the brain, involved in the processing and adjustment of pain stimuli, especially the emotion-motivational part of pain. The morphological plasticity of the hippocampus and the changes of neurochemicals in the hippocampus are closely related to pain, but the mechanism is not completely clear. Serotonin 5-hydroxytryptamine 5-HT) and the 5-HT2A receptor are involved in pain mediation. Brain-derived neurotrophic factor (BDNF) can regulate the plasticity of hippocampal neurons. The purpose of this study was to investigate the expression of 5-HT-5-HT2A receptor mRNA and 5-HT2A receptor mRNA and BDNFmRNA in hippocampus of rats with inflammatory pain. (2) to explore the effect of doxetine on the expression of 5-HT-5-HT2A receptor mRNA and BDNFmRNA in the hippocampus of inflammatory rats.) to explore the relationship between 5-HT and BDNF. Methods: Seventy-two adult SD rats were randomly divided into control group (n = 18), inflammatory pain model group (n = 18) and inflammatory pain model group (n = 18). The inflammatory pain model was induced by subcutaneous injection of complete Freund's Adjuvant (100 渭 l) and normal saline (1: 1) into the left plantar of rats. Doxicetine 10 mg / kg 路dl) for 2 weeks and saline at the same dose for 2 weeks. Before modeling and 2 weeks after treatment, the changes of paw withdrawal threshold in left plantar of rats were detected by electronic pain measuring instrument. The depressive behavior of rats was detected by sugar water preference experiment and forced swimming experiment. The expression of 5-HT2A receptor mRNA and BDNFmRNA in hippocampus of different groups was detected by RT-PCR and the changes of 5-HT in hippocampus were detected by Elisa. Results: compared with the control group, the pain threshold and glucose water consumption rate in the inflammatory pain model group were lower than those in the control group, and the immobility time was increased. The difference was statistically significant (P 0.05). Compared with the inflammatory pain model group, the 50%PWT of the inflammatory pain model group was higher than that of the saline group, the consumption rate of sugar water was increased (P 0.05), and the time of immobility was decreased (P 0.01). In the inflammatory pain model group, compared with the control group, the expression of 5-HT in the hippocampus decreased P0.05A, and the average expression of 5-HT2A receptor mRNA in the hippocampus decreased, but there was no significant difference between the two groups. Compared with the saline group, the expression of 5-HT in hippocampus and the expression of 5-HT2A receptor mRNA and BDNFmRNA in hippocampus were increased in the inflammatory pain model group compared with that in the saline group. Conclusion: the decrease of pain threshold and depression-like manifestation in chronic inflammatory pain rats may be related to the decrease of 5-HT level and BDNFmRNA expression in hippocampus, and doloxetine can increase the pain threshold and improve depressive behavior in chronic inflammatory pain rats. The mechanism of 5-HT may play a role in the regulation of BDNF by increasing the expression of 5-HT-5-HT2A receptor mRNA and BDNFmRNA in hippocampus.
【學(xué)位授予單位】:濟(jì)寧醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R402
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